Binding of two bis-bipyridine minor groove binders to a DNA template in the presence of Cu2+ ions

Abstract Some diseases are associated with abnormally extended regions of triplet repeats. These repeating regions are an attractive target for both diagnostic and therapeutic goals. In an attempt to approach to this goal, we have focused on establishment of an allosteric binding mechanism, in which the binding of the ligand promotes the next ligand binding. In the previous study, we already reported that the ligand having the bipyridine unit for binding with Cu2+ and the Hoechst33258 for binding to A3T3 site displayed Cu2+- mediated assembly on the DNA with two A3T3 sites. In this study, we synthesized the new ligands containing two bipyridine units attached to Hoechst33258 by different length linkers. It was expected that the bipyridine-Cu2+ complexation would enhance assembly of a number of the lingand on the DNA sequence with repeating regions. UV spectroscopy has been used to demonstrate the binding of these ligands to a DNA template mediated by the complexation of Cu2+ ions.